Synthesis and evaluation of anticancer activity of novel andrographolide derivatives

Abstract

A series of 3,19-O-acetal derivatives of andrographolide (1) have been synthesized by protecting the hydroxyls at C-3 and C-19 through a novel route. All the derivatives were evaluated for in vitro anticancer activity. Among the synthesized derivatives, compounds 3, 3a, 3d, 3e, 7 and 8 showed potential cytotoxicity against human cancer cell lines A549 (lung), HeLa (cervical), ACHN (renal), B-16 (melanoma) and IEC-6 (small intestine). The binding mode conformation was evaluated through docking simulations, while bioavailability/drug-likeness was evaluated through predictive ADME screening studies. All the derivatives were characterized by spectroscopy and the stereochemistry of compounds 3a and 3e was also confirmed by X-ray analysis.

Synthesis of thioether andrographolide derivatives and their inhibitory effect against cancer cells

“…Furthermore, for the purpose of understanding the effects of electron-withdrawing and electron-donating groups, different thioether andrographolide derivatives substituted with fluorobenzene, nitrobenzene, methylbenzene, and methoxylbenzene were synthesized using the same strategy. The removal of the isopropylidene group of I (1-9) was carried out by employing AcOH/H 2 O to readily furnish the target compounds II (10)(11)(12)(13)(14)(15)(16)(17)(18).…”

“…In recent years, scientists have revealed that andrographolide and its derivatives possess anticancer activity both in vitro and in vivo. 2,[11][12][13][14][15][16][17][18][19] The mechanism of the antitumor actions is mainly through induction of cell cycle arrest and promotion of apoptosis in human cancer cells by attenuating various cell signaling pathways. [12][13][14] A series of andrographolide derivatives has been previously synthesized to screen their in vitro cytotoxicity against cancer cells.…”

“…2,[11][12][13][14][15][16][17][18][19] The mechanism of the antitumor actions is mainly through induction of cell cycle arrest and promotion of apoptosis in human cancer cells by attenuating various cell signaling pathways. [12][13][14] A series of andrographolide derivatives has been previously synthesized to screen their in vitro cytotoxicity against cancer cells. [4][5][6][7] Based on previous studies, the γ-lactone moiety, the conjugated double bonds, CO, and the C-14 hydroxyl group play important roles in cytotoxicity.…”

“…In continuation of our studies on antitumor natural products, we chose andrographolide as the lead compound to design and synthesize more potent and active antitumor derivatives. Based on previously reported structure-activity relationship studies, [4][5][6][7]11,[13][14][15][16][17][18][19] we focused our effort on the development of 14-OH and C-12 derivatives of andrographolide. We envisaged that introduction of different aromatic (or heteroaromatic) thioethers into C-12 or 14-OH might increase hydrogen bonding and π-π stacking interactions and thereby have better effects on the hydrophilic and antitumor properties.…”

Synthesis of non‐toxic anticancer active forskolin‐indole‐triazole conjugates along with their in silico succinate dehydrogenase inhibition studies

“…Our earlier studies on the cyclic acetal protection of hydroxyls of forskolins and andrographolides with suitable functional groups, significantly increased its cytotoxicity [41][42][43]. In view of the above finding, it is envisaged that synthesis of a hybrid of forskolin-indole-1,2,3triazole (FIT) and its anlogues may result in high value, potent, selective and less toxic bioactive molecules.…”